Stem Cell Reports最新文献_第6页

Ras promotes germline stem cell division in Drosophila ovaries. Ras 促进果蝇卵巢生殖干细胞分裂

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-18 DOI: 10.1016/j.stemcr.2024.06.005

Qi Zhang, Yanfang Wang, Zhenan Bu, Yang Zhang, Qian Zhang, Le Li, Lizhong Yan, Yuejia Wang, Shaowei Zhao

{"title":"Ras promotes germline stem cell division in Drosophila ovaries.","authors":"Qi Zhang, Yanfang Wang, Zhenan Bu, Yang Zhang, Qian Zhang, Le Li, Lizhong Yan, Yuejia Wang, Shaowei Zhao","doi":"10.1016/j.stemcr.2024.06.005","DOIUrl":"10.1016/j.stemcr.2024.06.005","url":null,"abstract":"The Ras family genes are proto-oncogenes that are highly conserved from Drosophila to humans. In Drosophila, RasV12 is a constitutively activated form of the Ras oncoprotein, and its function in cell-cycle progression is context dependent. However, how it influences the cell cycle of female germline stem cells (GSCs) still remains unknown. Using both wild-type GSCs and bam mutant GSC-like cells as model systems, here we determined that RasV12 overexpression promotes GSC division, not growth, opposite to that in somatic wing disc cells. Ras performs this function through activating the mitogen-activated protein kinase (MAPK) signaling. This signaling is activated specifically in the M phase of mitotic germ cells, including both wild-type GSCs and bam mutant GSC-like cells. Furthermore, RasV12 overexpression triggers polyploid nurse cells to die through inducing mitotic stress. Given the similarities between Drosophila and mammalian GSCs, we propose that the Ras/MAPK signaling also promotes mammalian GSC division.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1205-1216"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of consanguinity on the design of iPSC banks. 近亲结婚对 iPSC 库设计的影响。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-11 DOI: 10.1016/j.stemcr.2024.06.004

Imen F Alkuraya, Edward B De Vol

引用次数: 0

Advanced human embryo research beyond the 14-day limit: A bioethical perspective from the Muslim world. 超过 14 天限制的先进人类胚胎研究：穆斯林世界的生物伦理视角。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.008

Mohammed Ghaly, Essam M Abdelalim

引用次数: 0

Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart. 移植的多能干细胞衍生心肌细胞的脉冲启动可刺激受体心脏。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.012

Tim Stüdemann, Barbora Schwarzová, Till Schneidewind, Birgit Geertz, Constantin von Bibra, Marie Nehring, Judith Rössinger, J Simon Wiegert, Thomas Eschenhagen, Florian Weinberger

{"title":"Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart.","authors":"Tim Stüdemann, Barbora Schwarzová, Till Schneidewind, Birgit Geertz, Constantin von Bibra, Marie Nehring, Judith Rössinger, J Simon Wiegert, Thomas Eschenhagen, Florian Weinberger","doi":"10.1016/j.stemcr.2024.06.012","DOIUrl":"10.1016/j.stemcr.2024.06.012","url":null,"abstract":"Transplantation of pluripotent stem cell-derived cardiomyocytes is a novel promising cell-based therapeutic approach for patients with heart failure. However, engraftment arrhythmias are a predictable life-threatening complication and represent a major hurdle for clinical translation. Thus, we wanted to experimentally study whether impulse generation by transplanted cardiomyocytes can propagate to the host myocardium and overdrive the recipient rhythm. We transplanted human induced pluripotent stem cell-derived cardiomyocytes expressing the optogenetic actuator Bidirectional Pair of Opsins for Light-induced Excitation and Silencing (BiPOLES) in a guinea pig injury model. Eight weeks after transplantation ex vivo, Langendorff perfusion was used to assess electrical coupling. Pulsed photostimulation was applied to specifically activate the engrafted cardiomyocytes. Photostimulation resulted in ectopic pacemaking that propagated to the host myocardium, caused non-sustained arrhythmia, and stimulated the recipient heart with higher pacing frequency (4/9 hearts). Our study demonstrates that transplanted cardiomyocytes can (1) electrically couple to the host myocardium and (2) stimulate the recipient heart. Thus, our results provide experimental evidence for an important aspect of engraftment-induced arrhythmia induction and thereby support the current hypothesis that cardiomyocyte automaticity can serve as a trigger for ventricular arrhythmias.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1053-1060"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

JAK/STAT signaling promotes the emergence of unique cell states in ulcerative colitis. JAK/STAT 信号转导促进了溃疡性结肠炎独特细胞状态的出现。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-18 DOI: 10.1016/j.stemcr.2024.06.006

Grzegorz Maciag, Stine Lind Hansen, Kata Krizic, Lauge Kellermann, Maureen Joy Inventor Zøylner, Svetlana Ulyanchenko, Martti Maimets, Astrid Møller Baattrup, Lene Buhl Riis, Konstantin Khodosevich, Toshiro Sato, Raul Bardini Bressan, Ole Haagen Nielsen, Kim B Jensen

{"title":"JAK/STAT signaling promotes the emergence of unique cell states in ulcerative colitis.","authors":"Grzegorz Maciag, Stine Lind Hansen, Kata Krizic, Lauge Kellermann, Maureen Joy Inventor Zøylner, Svetlana Ulyanchenko, Martti Maimets, Astrid Møller Baattrup, Lene Buhl Riis, Konstantin Khodosevich, Toshiro Sato, Raul Bardini Bressan, Ole Haagen Nielsen, Kim B Jensen","doi":"10.1016/j.stemcr.2024.06.006","DOIUrl":"10.1016/j.stemcr.2024.06.006","url":null,"abstract":"The intestinal epithelium ensures uptake of vital nutrients and acts as a barrier between luminal contents and the underlying immune system. In inflammatory bowel diseases, such as ulcerative colitis (UC), this barrier is compromised, and patients experience debilitating symptoms. Here, we perform single-cell RNA profiling of epithelial cells and outline patterns of cell fate decisions in healthy individuals and UC patients. We demonstrate that patterns of hierarchical behavior are altered in UC patients and identify unique cellular states associated with Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation in ulcerated and non-ulcerated areas of the colonic epithelium. These transcriptional changes could be recapitulated in human colonic organoids, wherein cytokine-mediated activation of JAK/STAT led to the emergence of cell populations with augmented regenerative properties. Altogether, our findings indicate that intricate relationships between epithelial and cytokine signaling regulate cell fate during epithelial tissue regeneration in humans and have important implications for the understanding of UC biology.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1172-1188"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human microglia-derived proinflammatory cytokines facilitate human retinal ganglion cell development and regeneration. 人类小胶质细胞衍生的促炎细胞因子促进了人类视网膜神经节细胞的发育和再生。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.009

Murali Subramani, Brandon Lambrecht, Iqbal Ahmad

{"title":"Human microglia-derived proinflammatory cytokines facilitate human retinal ganglion cell development and regeneration.","authors":"Murali Subramani, Brandon Lambrecht, Iqbal Ahmad","doi":"10.1016/j.stemcr.2024.06.009","DOIUrl":"10.1016/j.stemcr.2024.06.009","url":null,"abstract":"Microglia (μG), the resident immune cells in the central nervous system, surveil the parenchyma to maintain the structural and functional homeostasis of neurons. Besides, they influence neurogenesis and synaptogenesis through complement-mediated phagocytosis. Emerging evidence suggests that μG may also influence development through proinflammatory cytokines. Here, we examined the premise that tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), the two most prominent components of the μG secretome, influence retinal development, specifically the morphological and functional differentiation of human retinal ganglion cells (hRGCs). Using controlled generation of hRGCs and human μG (hμG) from pluripotent stem cells, we demonstrate that TNF-α and IL-1β secreted by unchallenged hμG did not influence hRGC generation. However, their presence significantly facilitated neuritogenesis along with the basal function of hRGCs, which involved the recruitment of the AKT/mTOR pathway. We present ex vivo evidence that proinflammatory cytokines may play an important role in the morphological and physiological maturation of hRGCs, which may be recapitulated for regeneration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1092-1106"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q. 人类多能干细胞的无饲养培养驱动了 MDM4 介导的 1q 染色体增益。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-03 DOI: 10.1016/j.stemcr.2024.06.003

Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley, Johanna Zerbib, Duncan Baker, Amy L Harding, Lydia H Jestice, Thomas F Eleveld, Ad J M Gillis, Sanne Hillenius, Leendert H J Looijenga, Paul J Gokhale, Uri Ben-David, Tenneille E Ludwig, Ivana Barbaric

{"title":"Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.","authors":"Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley, Johanna Zerbib, Duncan Baker, Amy L Harding, Lydia H Jestice, Thomas F Eleveld, Ad J M Gillis, Sanne Hillenius, Leendert H J Looijenga, Paul J Gokhale, Uri Ben-David, Tenneille E Ludwig, Ivana Barbaric","doi":"10.1016/j.stemcr.2024.06.003","DOIUrl":"10.1016/j.stemcr.2024.06.003","url":null,"abstract":"Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1217-1232"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human microglial cells as a therapeutic target in a neurodevelopmental disease model. 将人类小胶质细胞作为神经发育疾病模型的治疗靶点

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.013

Pinar Mesci, Christopher N LaRock, Jacob J Jeziorski, Hideyuki Nakashima, Natalia Chermont, Adriano Ferrasa, Roberto H Herai, Tomoka Ozaki, Aurian Saleh, Cedric E Snethlage, Sandra Sanchez, Gabriela Goldberg, Cleber A Trujillo, Kinichi Nakashima, Victor Nizet, Alysson R Muotri

{"title":"Human microglial cells as a therapeutic target in a neurodevelopmental disease model.","authors":"Pinar Mesci, Christopher N LaRock, Jacob J Jeziorski, Hideyuki Nakashima, Natalia Chermont, Adriano Ferrasa, Roberto H Herai, Tomoka Ozaki, Aurian Saleh, Cedric E Snethlage, Sandra Sanchez, Gabriela Goldberg, Cleber A Trujillo, Kinichi Nakashima, Victor Nizet, Alysson R Muotri","doi":"10.1016/j.stemcr.2024.06.013","DOIUrl":"10.1016/j.stemcr.2024.06.013","url":null,"abstract":"Although microglia are macrophages of the central nervous system, their involvement is not limited to immune functions. The roles of microglia during development in humans remain poorly understood due to limited access to fetal tissue. To understand how microglia can impact human neurodevelopment, the methyl-CpG binding protein 2 (MECP2) gene was knocked out in human microglia-like cells (MGLs). Disruption of the MECP2 in MGLs led to transcriptional and functional perturbations, including impaired phagocytosis. The co-culture of healthy MGLs with MECP2-knockout (KO) neurons rescued synaptogenesis defects, suggesting a microglial role in synapse formation. A targeted drug screening identified ADH-503, a CD11b agonist, restored phagocytosis and synapse formation in spheroid-MGL co-cultures, significantly improved disease progression, and increased survival in MeCP2-null mice. These results unveil a MECP2-specific regulation of human microglial phagocytosis and identify a novel therapeutic treatment for MECP2-related conditions.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1074-1091"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed. 胎儿造血干细胞/祖细胞的克隆分析揭示了移植后能力的分布情况。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-08-01 DOI: 10.1016/j.stemcr.2024.07.003

Olivia J Stonehouse, Christine Biben, Tom S Weber, Alexandra Garnham, Katie A Fennell, Alison Farley, Antoine F Terreaux, Warren S Alexander, Mark A Dawson, Shalin H Naik, Samir Taoudi

{"title":"Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed.","authors":"Olivia J Stonehouse, Christine Biben, Tom S Weber, Alexandra Garnham, Katie A Fennell, Alison Farley, Antoine F Terreaux, Warren S Alexander, Mark A Dawson, Shalin H Naik, Samir Taoudi","doi":"10.1016/j.stemcr.2024.07.003","DOIUrl":"10.1016/j.stemcr.2024.07.003","url":null,"abstract":"It has been proposed that adult hematopoiesis is sustained by multipotent progenitors (MPPs) specified during embryogenesis. Adult-like hematopoietic stem cell (HSC) and MPP immunophenotypes are present in the fetus, but knowledge of their functional capacity is incomplete. We found that fetal MPP populations were functionally similar to adult cells, albeit with some differences in lymphoid output. Clonal assessment revealed that lineage biases arose from differences in patterns of single-/bi-lineage differentiation. Long-term (LT)- and short-term (ST)-HSC populations were distinguished from MPPs according to capacity for clonal multilineage differentiation. We discovered that a large cohort of long-term repopulating units (LT-RUs) resides within the ST-HSC population; a significant portion of these were labeled using Flt3-cre. This finding has two implications: (1) use of the CD150+ LT-HSC immunophenotype alone will significantly underestimate the size and diversity of the LT-RU pool and (2) LT-RUs in the ST-HSC population have the attributes required to persist into adulthood.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1189-1204"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening. 微重力条件下的芯片骨骼肌作为再生建模和药物筛选平台。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-08-13 Epub Date: 2024-07-25 DOI: 10.1016/j.stemcr.2024.06.010

Soochi Kim, Bugra Ayan, Mahdis Shayan, Thomas A Rando, Ngan F Huang

{"title":"Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening.","authors":"Soochi Kim, Bugra Ayan, Mahdis Shayan, Thomas A Rando, Ngan F Huang","doi":"10.1016/j.stemcr.2024.06.010","DOIUrl":"10.1016/j.stemcr.2024.06.010","url":null,"abstract":"Microgravity has been shown to lead to both muscle atrophy and impaired muscle regeneration. The purpose was to study the efficacy of microgravity to model impaired muscle regeneration in an engineered muscle platform and then to demonstrate the feasibility of performing drug screening in this model. Engineered human muscle was launched to the International Space Station National Laboratory, where the effect of microgravity exposure for 7 days was examined by transcriptomics and proteomics approaches. Gene set enrichment analysis of engineered muscle cultured in microgravity, compared to normal gravity conditions, highlighted a metabolic shift toward lipid and fatty acid metabolism, along with increased apoptotic gene expression. The addition of pro-regenerative drugs, insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i), partially inhibited the effects of microgravity. In summary, microgravity mimics aspects of impaired myogenesis, and the addition of these drugs could partially inhibit the effects induced by microgravity.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1061-1073"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0